Engineering Tumor Cells with Tumor Necrosis Factor α (TNF-α) or CD40 Ligand (CD40L) Genes Induce Anti-tumor Immune Responses

Daneshmandi, Saeed and Shahrokhi, Somayeh (2018) Engineering Tumor Cells with Tumor Necrosis Factor α (TNF-α) or CD40 Ligand (CD40L) Genes Induce Anti-tumor Immune Responses. International Journal of Peptide Research and Therapeutics.

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Official URL: https://link.springer.com/article/10.1007%2Fs10989...

Abstract

One of the main problems in tumor therapy is immunosuppressive microenvironment of the tumor. To overcome this, we assessed targeted tumor cells with tumor necrosis factor-α (TNF-α) or CD40 Ligand (CD40L) to improve antigen presenting cells function and subsequently anti-tumor responses. 4T1 tumor cells were transfected with TNF-α and CD40L genes using lipofectamine and chitosan nanocomplexes. Engineered tumor cells were assessed in vitro and in vivo. Results showed that chitosan nanoparticles delivery of TNF-α or CD40L to 4T1 co-cultured with DCs induced expression of DCs co-stimulatory markers and enhanced the secretion of pro-inflammatory mediators IL-6, TNF-α and IL-12. The DCs were also able to enhance expansion of T cells with enhanced IFN-γ and decreased IL-4 production. TNF-α or CD40L engineered 4T1 cells resulted into delay in tumor growth. The study shows that nanoparticle manipulation of tumor cells by TNF-α or CD40L induce anti-tumor immune responses. Then, strategies that apply chitosan nanoparticles could provide a potent tool for tumor targeting and treatments.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
R Medicine > RB Pathology
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: sobhan rezaiian
Date Deposited: 29 May 2018 04:35
Last Modified: 29 May 2018 04:35
URI: http://eprints.lums.ac.ir/id/eprint/1301

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